2023年10月27日，来自中国科学院动物研究所刘光慧等研究人员合作在《细胞—干细胞》杂志上发表了标题为“ Decoding aging-dependent regenerative decline across tissues at single-cell resolution.”的研究成果，发现以单细胞分辨率解码衰老依赖性组织再生衰退。
据悉，各个组织和器官的再生能力差异很大，并随着年龄的增长而逐渐下降。
为了解读衰老与再生能力之间的关系，研究人员对来自年轻和衰老小鼠的八个组织的再生进行了全面的单细胞转录组分析。研究人员采用了多种分析模型来研究组织再生，并揭示了衰老组织再生过程减弱的复杂细胞和分子机制。具体来说，研究人员发现干细胞流动性受损和血管生成不足是造成与年龄相关的再生能力下降的主要原因。
此外，研究人员还发现了一个独特的Arg1+巨噬细胞亚群，它们在年轻组织中被激活，但在衰老再生组织中却被抑制，这表明它们在再生过程中与年龄相关的免疫反应差异中发挥着重要作用。这项研究提供了一个全面的单细胞资源，可用于确定潜在的干预目标，以提高老龄人口的再生效果。
该研究首次在系统水平解码了不同组织再生过程中的动态变化规律，阐明了增龄所致组织再生能力减损的细胞和分子机制，建立了再生和衰老的全新关联，揭示了调控哺乳动物再生的潜在细胞和分子靶标，为探讨多组织再生规律、剖析增龄导致的再生障碍，提供了宝贵的资源。此外，该研究鉴定出一类新型Arg1+巨噬细胞亚群，可能通过促进血管生成，参与促进组织损伤后的重塑和修复，提示靶向特定巨噬细胞有望干预衰老相关再生障碍，为发展延缓衰老的新策略提供了思路。该研究为实现组织器官修复、预防和治疗衰老相关疾病奠定了重要的理论基础
Highlights
•Aging impairs tissue regeneration across multiple organs
•Single-cell transcriptomics uncovers regeneration dynamics in young and aged tissues
•Systemic comparison reveals molecular mechanisms for this age-related decline
•These include impaired stem cell mobility, angiogenesis, and Arg1+ macrophage burst
Summary
Regeneration across tissues and organs exhibits significant variation throughout the body and undergoes a progressive decline with age. To decode the relationships between aging and regenerative capacity, we conducted a comprehensive single-cell transcriptome analysis of regeneration in eight tissues from young and aged mice. We employed diverse analytical models to study tissue regeneration and unveiled the intricate cellular and molecular mechanisms underlying the attenuated regenerative processes observed in aged tissues. Specifically, we identified compromised stem cell mobility and inadequate angiogenesis as prominent contributors to this age-associated decline in regenerative capacity. Moreover, we discovered a unique subset of Arg1+ macrophages that were activated in young tissues but suppressed in aged regenerating tissues, suggesting their important role in age-related immune response disparities during regeneration. This study provides a comprehensive single-cell resource for identifying potential targets for interventions aimed at enhancing regenerative outcomes in the aging population.
文章来源：
Yusheng Cai, Muzhao Xiong, Zijuan Xin et al, Decoding aging-dependent regenerative decline across tissues at single-cell resolution. DOI: 10.1016/j.stem.2023.09.014，Cell Stem Cell：最新IF：25.269
